Back to basics: label-free technologies for small molecule screening

Small molecule high-throughput screening in drug discovery today is dominated by techniques which are dependent upon artificial labels or reporter systems. While effective, these approaches can be affected by certain experimental limitations, such as conformational restrictions imposed by the selected label or compound fluorescence/quenching. Label-free approaches potentially address many of these issues by allowing researchers to investigate more native systems without fluorescence- or luminescence-based readouts. However, due to throughput and expense constraints, label-free methods have been largely relegated to a supporting role as the basis of secondary assays. In this review, we describe recent improvements in impedance-based, optical biosensor-based, automated patch clamp and mass spectrometry technologies that have enhanced their ease of use and throughput and, hence, their utility for primary screening of small- to medium-sized compound libraries. The ultimate maturation of these techniques will enable drug discovery researchers to screen large chemical libraries against minimally manipulated biological systems.     

Polarization-multiplexed vibrational sum frequency generation for comprehensive simultaneous characterization of interfaces

We describe a novel three-pulse experimental arrangement for the simultaneous generation and subsequent resolution of all four electric-dipole allowed vibrational sum frequency generation polarization combinations. For noncentrosymmetric and achiral systems, this represents full characterization of all symmetry-allowed elements of the second-order susceptibility, providing a comprehensive intensity level assessment of the system under study. By measuring all relevant signals simultaneously, this approach enables assessment of molecular orientation and structure in dynamic, temporally evolving systems that were previously inaccessible by means of sequentially scanned acquisition of the individual tensor elements.     

Transfer measurements for the Ti+Ni systems at near barrier energies

Large enhancements have been observed in the sub-barrier fusion cross sections for Ti+Ni systems in our previous studies. Coupled channel calculations incorporating couplings to 2⁺ and 3⁻ states failed to explain these enhancements completely. A possibilty of transfer channels contributing to the residual enhancements had been suggested. In order to investigate the role of relevant transfer channels, measurements of one- and two-nucleon transfer were carried out for ^46,48Ti+⁶¹Ni systems. The present paper gives the results of these studies.     

Generalized minimizing movements for the mean curvature flow with Dirichlet boundary condition

We study a variational approach, called Generalized Minimizing Movemenents (GMM) and proposed by E. De Giorgi, to evolution of hypersurfaces by mean curvature in the case of a Dirichlet boundary datum. We prove an existence theorem of a GMM when on the initial solid are made suitable geometric hypotheses.

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Sunto Si studia un approccio variazionale, detto Movimenti Minimizzanti Generalizzati (GMM) e proposto da Ennio De Giorgi, per l’evoluzione di una ipersuperficie secondo la curvatura media con un dato al bordo di tipo Dirichlet. Viene provato un teorema di esistenza quando sul solido iniziale siano fatte opportune ipotesi di tipo geometrico.

     

A variational approach to mean curvature flow with Dirichlet conditions

We study a variational approach, called Generalized Minimizing Movements (GMM), to evolution of hypersurfaces by mean curvature in the case of a Dirichlet boundary datum. We prove an existence theorem of a GMM when on the initial solid are made suitable geometric hypotheses.

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Sunto In questo lavoro studiamo un approccio variazionale, detto Movimenti Minimizzanti Generalizzati (GMM), all’evoluzione di ipersuperfici per curvatura media nel caso di dato al bordo di Dirichlet. Dimostriamo un teorema di esistenza per un GMM quando vengono assunte ipotesi opportune sul solido iniziale.

     

Causal loop diagrams as a de-escalation technique

Escalation of commitment, the tendency of decision makers to keep on investing in losing courses of action, has been shown to be a costly decision bias that affects many areas of decision making. Even though escalation is a widely studied phenomenon, there has been comparatively little research on how to avoid this bias. The present study focuses on de-escalation of commitment and proposes that causal loop diagrams (CLDs) can help to decrease escalating commitment to a failing course of action. By means of an experiment, this study shows that using a CLD decreases escalation tendencies.